INTRODUCTION — The diagnosis and treatment of plica syndrome will be reviewed here. The causes and diagnostic approach to knee pain in the young athlete and adults are discussed separately:

See “Approach to acute knee pain and injury in children and skeletally immature adolescents”

See “Approach to chronic knee pain or injury in children or skeletally immature adolescents”

See “Approach to the adult with unspecified knee pain”

See “Physical examination of the knee”

See “Approach to the adult with knee pain likely of musculoskeletal origin”

DEFINITION — Plica syndrome is a painful condition of the knee, often reported in runners and other athletes. The abnormal plica, an intraarticular band of thick, fibrotic tissue, may cause pain and a popping sensation by rubbing across either the medial femoral condyle or undersurface of the patella.

ANATOMY AND CLASSIFICATION — Plicae are considered to be normal mesenchymal structures that represent remnants of the septations created by the various cavitations that coalesce to form the knee joint in utero. These septations begin to involute about the 12th week of fetal life, but they persist in up to 50 percent of individuals based upon autopsy findings [1,2].

The normal plica is seen arthroscopically to be a thin, vascular structure that is easily deformable with a probe, often appearing as a thin, narrow veil of tissue. An abnormal plica is thick, fibrotic, and relatively avascular, at least in its mid-portion, and is often taut and cord-like.

There are four distinct types of plica based on their origin and insertion (figure 1):

The suprapatellar plica lies between the suprapatellar bursa and the knee joint [3]. Incidence of normal plica in arthroscopically operated knees approaches 87 to 91 percent.

The medial plica (also called the medial shelf, plica synovialis mediopatellaris, plica alaris elongata, lion’s bands, or Aoki edge) arises from the medial wall of the knee joint, passes down and around the medial femoral epicondyle, and inserts into the synovium surrounding the infrapatellar fat pad [2,3]. This plica appears normally in 55 to 92 percent of arthroscopically knees depending on how the plica was defined [4].

The infrapatellar plica (or ligamentum mucosum) arises from the intercondylar notch and inserts into the synovium surrounding the infrapatellar fat pad [2,3]. A normal infrapatellar plica is also commonly found at arthroscopy, with one series finding it in 86 percent of patients [5].

The lateral plica occurs rarely [2,3]. It was found in less than 1 percent of 400 patients undergoing arthroscopy in one series [5].

It is common for an individual to have more than one plica. There are no distinct combinations of multiple plica [5].

Medial plicae are most commonly symptomatic. As an example, in one series of 400 knees explored arthroscopically for knee pain without other major cartilage, ligament, or bone derangement, 72 percent of patients had medial patellar plicae [5]. Of these, 60 percent were type C (shelf) according to their classification.

A classification system based upon morphology has been developed for each type of plica (ie, suprapatellar, medial patellar, infrapatellar, and lateral patellar). As an example, the following morphologic designations are common for medial patellar plica [5]:

(A) Absent

(B) Vestigial – A line of elevation 1 mm or less arises from the medial synovial shelf

EPIDEMIOLOGY — The prevalence of symptomatic (presumably abnormal) plica is not known, primarily due to the absence of strict clinical criteria for making this diagnosis. However, it is described in a variety of age groups from children to adults [2]. Many experts suggest that plica syndrome is an under-diagnosed cause of anterior knee pain in adolescents and young adults. Estimates for the frequency of plica syndrome based upon small arthroscopic series of children, adolescents and young adults with acute knee pain range from 8 to 45 percent [6-8]. An abnormal medial plica was most commonly found.

The plica syndrome has most often been reported in runners in whom repetitive motion combined with abnormal motion or biomechanical stress at the knee joint causes excessive anterior contact between the medial plica and either the medial femoral condyle or medial patellar facet. Symptomatic plicae also occur in swimmers, rowers, cyclers, and basketball players [9]. Furthermore, a plica may become symptomatic in the absence of a history of trauma or intraarticular pathology, especially in patients with a knee valgus. (See ‘Physical examination’ below.)

PATHOPHYSIOLOGY — Pathologically abnormal plica may develop after direct trauma (eg, a direct blow to the knee or twisting injury), or following repetitive knee movements that cause injury and inflammation of the plica with subsequent fibrosis [3,10]. Intraarticular abnormalities, such as loose foreign bodies osteochondritis dissecans, or inflammatory arthritis may also inflame a plica. The resulting thickening and loss of elasticity of the structure causes it to snap over the medial femoral condyle causing synovitis, chondral damage, and pain.

CLINICAL MANIFESTATIONS

History — Individuals with symptomatic plica often complain of anterior and medial knee pain [3]. Some patients report that this pain began with a direct blow or twisting injury to the knee. They frequently describe the pain as worse with activity, such as running, squatting, going up or down stairs, or kneeling, and after prolonged sitting (cinema sign). The pain is often accompanied by a popping sensation with knee flexion. Patients may also report clicking, catching, knee pseudo-locking (false locking), or giving way. In most patients, only one knee is involved.

Physical examination — Findings of plica syndrome are often nonspecific and include the following in symptomatic patients:

Palpable fibrotic fold or cord over the medial femoral condyle (medial plica) that is painful when the knee is either in full extension or is flexed [11]; this finding is not specific for medial plica syndrome [12,13].

Effusion; joint swelling typically indicates the presence of chondral injury associated with a plica and is frequent in adults but uncommon in adolescent patients [15].

Reproduction of clicking or popping with active or passive range of motion; this finding is rare.

Abnormalities of lower extremity alignment which predispose to plica may also be present upon inspection of the lower extremity:

Genu valgus or knock knees (figure 2) will tend to worsen the tension of the medial plica as it passes obliquely over the medial femoral condyle in the coronal plane and is a predisposing finding.

Abnormalities at the ankle and hip that cause valgus angulation at the knee during activity may contribute to the pain and clicking. These include weakness of the hip abductors or tight hip adductors.

Predisposing abnormalities of the foot include loss of longitudinal arch from posterior tibial dysfunction or spring ligament insufficiency leading to resting pronation at midfoot associated with subtalar subluxation or calcaneal valgus at the rear foot (picture 1) or congenital changes such as tarsal coalitions.

Provocative tests — In addition to the above clinical findings, the following provocative tests are helpful in making a diagnosis of plica syndrome:

Medial patellar plica (MPP) test – With the patient in the supine position, pressure is applied with the thumb over the inferior and medial aspect of the patellofemoral joint with the aim of interposing the medial plica between the medial patellar facet and the medial condyle [16]. While maintaining this pressure, the knee is passively flexed from 0 to 90 degrees (figure 3). Pain in extension that is relieved at 90 degrees of flexion constitutes a positive test.

In a meta-analysis of seven studies (492 knees), the MPP test had a sensitivity, specificity, and positive predictive value for medial plica syndrome of 90 and 89, percent, respectively, when performed by an orthopedist [17].

Knee extension test (Hughston test) – With the patient supine, starting with the knee at 90 degrees of flexion, one hand applies pressure on the lateral patella moving it medially, while the examiner internally rotates the lower leg then slowly extends the knee (figure 4) [18]. The test is positive if the patient’s pain and popping are reproduced between 60 and 45 degrees of flexion. This test was positive in all of 136 patients with symptomatic plicae in one series [14]. However, in the author’s experience, the knee extension test is helpful but not always positive in patients with plica syndrome.

Imaging — Plica syndrome is a clinical and arthroscopic diagnosis. However, imaging is frequently required to exclude other causes of knee pain. The type of imaging performed is determined by the leading alternative diagnoses. (See ‘Differential diagnosis’ below.)

In the patient with plica syndrome without other intraarticular or joint pathology, such as synovitis, chondral injury or loose foreign body, plain radiographs of the knee are normal.

Although arthrogram, flexed knee arthrogram, routine or dynamic ultrasound (US), and magnetic resonance imaging (MRI) can all demonstrate the presence of plicae, some studies have found them unreliable in predicting which plica are pathologic at surgery [12,19,20]. A systematic review of seven studies (492 knees) found the MPP test had the greatest diagnostic accuracy when compared to US or MRI although the MPP was similar to dynamic US in terms of sensitivity [17]. However, none of the studies included in the review compared the accuracy of these tests when all are performed in the same patient.

In one series, dynamic ultrasonography with medial and lateral patella manipulation in 88 patients with clinical findings suggestive of medial plica syndrome had a sensitivity, specificity, and diagnostic accuracy of 90, 83, and 88 percent respectively when compared to arthroscopic diagnosis [21]. While not useful for identifying plica, static knee US may identify other causes for anterior or medial knee pain that exclude the diagnosis of plica syndrome. (See “Musculoskeletal ultrasound of the knee”.)

MRI becomes most useful when the clinician expects a possibility of intra-articular pathology causing pain that mimics plica syndrome.

DIAGNOSIS — The diagnosis of plica syndrome is primarily based upon clinical features and should only be made once other causes of knee pain have been excluded. It is suggested by the history of anterior and medial knee pain after direct trauma, twisting injury, or repetitive injury. The pain typically becomes worse with squatting, kneeling, going upstairs, or sitting for long periods of time (cinema sign). Clicking upon knee flexion may also occur.

Physical findings are variable and nonspecific. In patients having a symptomatic medial plica, there may be subtle soft tissue swelling just medial to the patellar border. Careful palpation with the knee either in full extension or at 90 degrees of flexion may reveal a firm, tender ridge of tissue running either perpendicular or obliquely to the medial border of the patellar. Examination may also reveal tight quadriceps and hamstring muscles and positive medial patellar plica (MPP) (figure 3), or knee extension (figure 4) tests.

While the MPP test has reasonable sensitivity and specificity, no single clinical test or maneuver is diagnostic of a pathologic plica. Bedside high-quality dynamic ultrasound may help establish the diagnosis of plica syndrome, but other imaging (eg, magnetic resonance imaging) is primarily performed to exclude other knee pathology [17]. (See ‘Clinical manifestations’ above and ‘Differential diagnosis’ below.)

Relief of symptoms after injection of anesthetic (eg, lidocaine) into the plica may also aid in diagnosis and differentiation from other conditions.

Arthroscopy provides a definitive diagnosis if a thickened, fibrotic plica is demonstrated but is only performed when other diagnoses are considered or when conservative treatment fails. In patients with medial plica syndrome, intraoperative flexion of the knee causes the fibrotic plica to snap over the medial femoral condyle. (See ‘Initial treatment’ below.)

DIFFERENTIAL DIAGNOSIS

Patellofemoral pain — Patellofemoral pain (or runner’s knee) describes anterior knee pain involving the patella and retinaculum that may arise from overuse, improper patella tracking during extension, or trauma. Several clinical features overlap with plica syndrome including pain with increased activity, particularly going up and down stairs, during squatting, or after prolonged sitting. Patients with patellofemoral pain also often have tight hamstring, quadriceps, and calf muscles, evidence of excessive knee valgus with single-leg squat, and associated hip abductor weakness and hindfoot varus or mid-foot pronation. (See “Patellofemoral pain”, section on ‘Clinical presentation and examination’.)

Unlike plica syndrome, patellofemoral pain does not typically manifest with clicking or popping unless there is an associated chondromalacia or subluxation of the patella. Effusion or synovitis does not usually occur, and the pain is usually localized to the medial or lateral patellar facets by direct palpation in full extension. Other features of patellofemoral pain and its treatment are discussed in detail separately. (See “Patellofemoral pain”, section on ‘Clinical presentation and examination’ and “Patellofemoral pain”, section on ‘Initial treatment’.)

Osteoarthritis — Individuals with osteoarthritis of the patellofemoral joint may also localize pain to the anterior medial knee, and complain of crepitus and clicking. Pain on palpation is usually localized to the patellar facets, and the patellar grind test is positive for crepitus. The grind test is performed with the examiner applying downward pressure on the patella with the knee extended, as the patella is gently moved medially and laterally. Osteoarthritis may also manifest with synovitis or effusion. (See “Clinical manifestations and diagnosis of osteoarthritis”, section on ‘Knee’.)

Clinical criteria for osteoarthritis of the knee include age >50 years, morning stiffness for less than 30 minutes, crepitus on active knee movement, and bony tenderness or enlargement. Plain radiographs may show a decrease in cartilage space with adjacent osteophytes and sclerosis. Limitation of full motion is often present. This diagnosis is usually made based upon clinical criteria and confirmed with standing knee films and special views as needed. However, questionable cases can be confirmed with magnetic resonance imaging (MRI) showing articular cartilage loss or definitively confirmed by arthroscopy. (See “Clinical manifestations and diagnosis of osteoarthritis”, section on ‘Diagnosis’.)

Management of osteoarthritis is discussed separately. (See “Overview of the management of osteoarthritis”.)

Patellar subluxation — Patellar subluxation refers to excessive lateral movement of the patella such that the patella comes completely or partially out of the trochlear groove. This may occur as a result of trauma or in patients with laxity. These patients often complain of knee pain and popping or clicking, and occasionally knee swelling, stiffness, or catching. Patellar subluxation differs on presentation from medial plica syndrome in a number of ways (see “Recognition and initial management of lateral patellar dislocations”, section on ‘Patellar subluxation’):

The history more often involves giving way followed by sharp pain that may be felt on both medial and lateral patellar border.

On examination, tenderness is more often along the edge of the patella medially and laterally rather than in the capsule as in medial plica.

The apprehension sign with lateral patellar displacement is the most significant physical finding; this sign is absent in medial plica syndrome.

Medial meniscus tear — Patients with a medial meniscus tear will usually report an acute inciting event, often involving some torquing or rotational movement under stress without direct trauma. True locking and giving way more commonly occur with significant meniscal tears and are more pronounced than the catching or clicking felt by patients with medial plica syndrome. Patients with medial meniscus tears typically have tenderness along the medial joint line and discomfort or a catching sensation on provocative tests, such as the McMurray (picture 2), Apley, Thessaly, or bounce home tests (figure 5). Patients with plica syndrome typically have pain along the medial capsule and above the joint line. McMurray or Thessaly tests that require rotation rarely cause much pain in plica syndrome but are generally the most painful ones in medial meniscus injury. Dynamic ultrasound (US) or MRI can also distinguish between a medial meniscus tear and medial plica syndrome if uncertainty remains after clinical evaluation. (See “Meniscal injury of the knee”, section on ‘Physical examination’ and “Meniscal injury of the knee”, section on ‘Imaging’.)

Pes anserinus pain syndrome (formerly anserine bursitis) or tendonitis — The history of pes anserine bursitis differs sufficiently so that this condition rarely is mistaken for medial plica syndrome. The patient with pes anserinus pain syndrome or tendonitis complains of medial knee pain and may report swelling. However, there is no clicking or popping, no catching or pseudo-locking. Examination also shows that the tenderness at the anatomical pes is below the location where patients experience medial plica syndrome. US identifies swelling in the pes bursa when imaging is used. (See “Bursitis: An overview of clinical manifestations, diagnosis, and management”, section on ‘Pes anserinus pain syndrome (formerly anserine bursitis)’.)

Osteochondritis dissecans — Osteochondritis dissecans (OCD) presents with insidious onset of knee pain and a history of heavy activity, similar to some patients with the plica syndrome. Patients with OCD may also report swelling. If the osteochondral lesion is stable, the patient rarely reports clicking or popping. However, the location of the pain may be similar to the plica syndrome, as >70 percent of these lesions occur on the medial femoral condyle. In some patients with OCD, there is palpable tenderness near the medial edge of the intercondylar notch with the knee in partial flexion. However, a positive medial patellar plica test is unlikely in patients with OCD. Plain radiographs can be utilized to help distinguish OCD from medial plica syndrome. OCD is usually evident on plain films (image 1), although sometimes only with a tunnel view, whereas with plica the plain films are normal. In the minority of patients in whom doubt still remains after examination and plain radiographs (persistent symptoms but normal plain radiographs), magnetic resonance imaging can provide a definitive diagnosis of OCD. (See “Osteochondritis dissecans (OCD): Clinical manifestations and diagnosis”, section on ‘Clinical manifestations’ and “Osteochondritis dissecans (OCD): Clinical manifestations and diagnosis”, section on ‘Magnetic resonance imaging’.)

INITIAL TREATMENT — The goals of treatment for plica syndrome are to reduce pain, strengthen the knee extensor muscles (quadriceps), mitigate mechanical factors that produce excessive knee valgus, and return the patient to as high a level of function as possible. The acute phase of treatment during the first week focuses on pain control; the subsequent recovery phase focuses on modification of biomechanical deficits.

Acute phase — Treatment during the first week of care includes the following:

Activity modification – Patients need to avoid activities that cause pain during rehabilitation. Most runners need to reduce running volumes and those with severe signs or symptoms (eg, limping) should curtail all running activities. Patients with less severe symptoms may modify their training by reducing the overall distance and avoiding running up hills or steps. Athletes can maintain aerobic fitness by using a stationary bicycle (recumbent or upright), an upper body cycle, or by swimming, water running, or other activities, provided they do not cause pain.

Nonsteroidal antiinflammatory drugs (NSAIDs) – NSAIDs (eg, ibuprofen 10 mg/kg every six hours, maximum dose 800 mg) may be used for short-term pain relief during the first three days. No studies have specifically evaluated the benefit of NSAIDs for the treatment of plica syndrome.

Ice application – Although formal studies are lacking, applying ice to the medial knee is regarded by most experts as a key aspect of acute treatment of plica syndrome. The plica, being a superficial structure, requires ice applications of only 10 to 15 minutes duration three to four times per day.

Corticosteroid injection – Evidence is limited regarding the benefits and outcomes of patients who receive corticosteroid injections for plica syndrome. Corticosteroid injections should notbe routinely performed. Sports medicine experts anecdotally note that there can be clinical benefit of corticosteroid injection either into the thickened plica or intra-articular injection [2,22,23]. Benefit seems greatest in the early phase of the syndrome. Some expert clinicians prefer early injection while others would wait until failure of other conservative measures. Our approach is to give a trial of conservative measures for two to four weeks before attempting corticosteroid injection.

From a theoretical basis corticosteroid injection directly into the plica has the potential to cause some atrophy of the thickened plical band [2,22,23]. On the other hand, improvement after injection may also aid in the diagnosis of a symptomatic plica.

Recovery phase — Treatment beyond the first week of care consists of physical therapy to address tightness and weakness of specific muscle groups and orthotics to correct heel valgus if present.

Approach — Limited observational evidence from two small case series suggests that exercises to increase knee extensor strength and flexibility of the quadriceps, hip adductors (eg, adductor magnus), gastrocnemius, and hamstring muscles are successful in treating patients with plica syndrome [1,14].

Stretching – Once the initial pain has subsided, we suggest that patients with plica syndrome perform daily or twice daily therapeutic stretching exercises of the quadriceps, hip adductors (eg, adductor magnus), gastrocnemius, and hamstring muscles under the guidance of physical therapists. Observational studies suggest that 40 to 78 percent of patients with a clinical diagnosis of plica syndrome will return to their previous level of function without pain within three to six months of initiating stretching [1,14]. In one study, the patients with the greatest gains in flexibility had better outcomes [14].

Quadriceps strengthening – Once the initial pain has subsided, we suggest that patients with plica syndrome perform quadriceps strengthening exercises under the guidance of a physical therapist. In one series of 63 patients with a clinical diagnosis of plica syndrome, knee extension exercises in addition to stretching of the quadriceps, hip adductors (eg, adductor magnus), gastrocnemius, and hamstring muscles resulted in a return to normal function in 86 percent of patients within three months [1].

Treatment of dynamicknee valgus – Patients with mechanical factors producing excessive knee valgus as determined by a single leg squat, including weak hip abductors, tight hip adductors and iliotibial band, should also undergo physical therapy to correct these problems.

Compression knee sleeves or braces can be offered; however in the author’s experience they may increase pressure on the anterior-medial knee thereby worsening pain, especially in patients with medial plica syndrome so should not be routinely used. If after office application they do provide relief to the patient, a clinical trial is reasonable.

FOLLOW-UP CARE — The patient should be followed at least monthly during the recovery phase and more frequently if improvement is lacking. If the patient reports recurrence or persistence of knee pain, assess the patient’s compliance with and response to the prescribed therapy.

Have the patient explain in detail the exercises they have been doing. When did they first see the physical therapist? How many times a week do they go to physical therapy? How often do they do their home program? Have the patient demonstrate some of the exercises. Ask about their tolerance of the therapy and quantify their cardiovascular workouts (eg, “I can ride the stationary bike for 10 minutes until my knee hurts” versus “I’m still running 25 miles per week”). Ask about previously aggravating activities and assess improvement.

If there is improvement, continue physical therapy until the patient can perform all exercises without pain, and then slowly reintroduce activities which previously caused pain (eg, running). Increase activity levels in a gradual, step-wise progression, until the patient achieves the desired level. If the symptoms are unchanged and the patient appears to be compliant with both therapy and activity modification, re-examine the patient to confirm the original diagnosis. Perform additional imaging to evaluate for other diagnoses that commonly cause antero-medial knee pain as clinically indicated. (See ‘Differential diagnosis’ above.)

If the compliant patient has not improved with three to six months of therapy, then orthopedic consultation is indicated to assess for another cause for the pain and, if plica syndrome is confirmed, to reinforce the physical therapy regimen.

INDICATIONS FOR ORTHOPEDIC REFERRAL — Based upon small observational studies, surgical intervention, consisting of complete arthroscopic excision of the fibrotic plica, is potentially indicated when 12 months of conservative treatment, consisting of stretching of the quadriceps, hip adductors (eg, adductor magnus), gastrocnemius, and hamstring muscles and strengthening of the quadriceps muscles has failed [15,22]. Arthroscopy should also be considered in cases of persistent knee effusion. Operative treatment provides significant improvement in approximately 90 percent of patients.

During arthroscopy, the entire joint must be evaluated for other fibrotic plica, chondral injury to the undersurface of the patella and the medial femoral condylar articular surface, as well as other possible derangements (eg, arthrosis, loose bodies, or osteochondritis dissecans) that may have led to the development of a pathologic plica. Of note the plica may grow back after excision but is usually not symptomatic any longer.

SUMMARY AND RECOMMENDATIONS

A plica is an embryonic remnant commonly present in the population. Normally it consists of a thin, vascular, pliable band of tissue that originates from the synovial wall and crosses the synovial joint. It may be located in the suprapatellar, medial, infrapatellar, or lateral compartments of the knee joint (figure 1). (See ‘Epidemiology’ above and ‘Anatomy and classification’ above.)

A plica becomes abnormal when, as a result of direct blunt trauma to the knee, repetitive injury, or irritation from some other intraarticular abnormality, it becomes thickened, fibrotic, avascular, and taut. Symptoms occur as the nonpliable band either snaps over the medial femoral condyle, or is entrapped between the patella and femoral condyle. (See ‘Definition’ above and ‘Pathophysiology’ above.)

Diagnosis of plica syndrome is suggested by the history of anterior and medial knee pain after direct trauma, twisting injury, or repetitive injury. The pain typically becomes worse with squatting, kneeling, going upstairs, or sitting for long periods of time (cinema sign). Clicking upon knee flexion may also occur. Physical findings are variable. In patients having a medial plica, there may be subtle soft tissue swelling just medial to the patellar border. Careful palpation with the knee at 90 degrees of flexion may reveal a firm, tender ridge of tissue running either parallel or slightly obliquely to the medial border of the patellar. Examination may also reveal tight quadriceps and hamstring muscles, and positive medial patellar plica (figure 3) and knee extension (figure 4) tests. (See ‘Diagnosis’ above and ‘Provocative tests’ above.)

Imaging does not establish the diagnosis of plica syndrome but is primarily performed to exclude other knee pathology. (See ‘Clinical manifestations’ above and ‘Differential diagnosis’ above.)

Corticosteroid injections should not be routinely performed. However, corticosteroid injection directly into the painful plica when the plica is readily palpable may be helpful when the above conservative measures have not provided relief in two to four weeks. (See ‘Acute phase’ above.)

Once the initial pain has subsided, we suggest that patients with plica syndrome perform the following under the guidance of physical therapists (Grade 2C):

Patients with plica syndrome exacerbated by heel valgus and mid-foot pronation should receive an orthotic with a medial wedge. (See ‘Recovery phase’ above.)

Compression knee sleeves may also be tried as an adjunctive therapy, although some patients may have increased pain when sleeves are applied. (See ‘Recovery phase’ above.)

If a patient compliant with activity restrictions and physical therapy exercises has not improved within three to six months of therapy, then orthopedic or sports medicine consultation is indicated to assess for another cause for the pain and, if plica syndrome is confirmed, to reinforce the physical therapy regimen. Surgical intervention, consisting of complete arthroscopic excision of the fibrotic plica, is potentially indicated when 12 months of conservative treatment has failed. (See ‘Indications for orthopedic referral’ above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Jorge E Gomez, MD, who contributed to an earlier version of this topic review.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.